Project Summary The planar chip format that is widespread is microfluidics is ideally suited for a number of applications by virtue of the ability to create complex structures and functionalities all on the same substrate. Nonetheless, planar chips are typically limited to creating two-dimensional extruded features. Fibers, meanwhile, are drawn structures that today only used as passive fluid conduits (capillaries) to transfer liquids from one platform to another. Here we propose to utilize fibers to create active microfluidic devices: multimaterial microfluidic fibers (MMMF) that are fabricated in a thermal drawing process, allowing formation of complex cross-sectional geometries using a variety of materials (polymers, metals, semiconductors) with micron to nanometer resolution, along meters of fiber. MMMF provides a complementary route to creating microfluidic devices that leverages new dimensions of freedom. To illustrate the concept of an active MMMF, we specifically propose to develop fibers that perform dielectrophoretic (DEP) cell separations, leveraging the fiber format to attain 1 ml/min mammalian cell separation in physiological buffer, which is 100-1000 faster than comparable devices. The approach is to use DEP forces to alter the particle equilibrium points that exist in inertial microfluidic flows, using the cross- sectional geometry of the fiber to allow for the creation of complex electrode geometry. Critically, advances in additive manufacturing now make it feasible to interface to fibers to send particles from separated flow streams to distinct outlets. Over the course of two Aims, we propose to first develop a MMMF capable of using DEP-modulated inertial forces to separate mammalian cells in physiological buffer at rates of 1 mL/min. We will then apply these fibers to separate immune cells based on their electrical signatures, which are correlated to immune cell activation state, and holds promise as a method to monitor the immune system during sepsis.